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10.1002/cmdc.201300134 http://scihub22266oqcxt.onion/10.1002/cmdc.201300134 23788528!3954986!23788528     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ChemMedChem 2013 ; 8 (8): 1361-72 Nephropedia Template TP {{tp|p=23788528|t=2013. Synergistic inhibitor binding to the papain-like protease of human SARS coronavirus: mechanistic and inhibitor design implications |pdf=|usr=}}{{23788528}} gab.com Text Synergistic inhibitor binding to the papain-like protease of human SARS coronavirus: mechanistic and inhibitor design implications JO: ChemMedChem http://www.kidney.de/pget.php?&tw=1&pmid=23788528 #FOAvip We previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus. In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next-generation compounds based on a computational fragment-merging approach. This approach provides an alternative strategy for lead optimization for cases in which direct co-crystallization is difficult. Twit Text FOAVip Synergistic inhibitor binding to the papain-like protease of human SARS coronavirus: mechanistic and inhibitor design implications ????ChemMedChem http://www.kidney.de/pget.php?&tw=1&pmid=23788528 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23788528 #FOAvip English Wikipedia <ref>{{Cite pmid|23788528}}</ref> Synergistic inhibitor binding to the papain-like protease of human SARS coronavirus: mechanistic and inhibitor design implications #MMPMID23788528 Lee H; Cao S; Hevener KE; Truong L; Gatuz JL; Patel K; Ghosh AK; Johnson ME ChemMedChem 2013[Aug]; 8 (8): 1361-72 PMID23788528show ga We previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus. In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next-generation compounds based on a computational fragment-merging approach. This approach provides an alternative strategy for lead optimization for cases in which direct co-crystallization is difficult. |*Drug Design[MESH] |Antiviral Agents/*chemistry/metabolism[MESH] |Binding Sites[MESH] |Coronavirus 3C Proteases[MESH] |Cysteine Endopeptidases/metabolism[MESH] |Drug Synergism[MESH] |Humans[MESH] |Kinetics[MESH] |Molecular Docking Simulation[MESH] |Protease Inhibitors/*chemistry/metabolism[MESH] |Protein Binding[MESH] |Protein Structure, Tertiary[MESH] |Severe acute respiratory syndrome-related coronavirus/*enzymology[MESH] |Small Molecule Libraries/chemistry/metabolism[MESH] |Surface Plasmon Resonance[MESH]Synergistic inhibitor binding to the papain-like protease of human SAR(epmc).pdf DeepDyve Pubget Overpricing